Kalafati, Marianthi, Kutmon, Martina, Evelo, Chris T., van der Kallen, Carla J.H., Schalkwijk, Casper G., Stehouwer, Coen D.A., Blaak, Ellen E., van Greevenbroek, Marleen M.J., Adriaens, Michiel, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke Jan, APH - Methodology, APH - Mental Health, Amsterdam Reproduction & Development, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Humane Biologie, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Maastricht Centre for Systems Biology, RS: FHML MaCSBio, RS: FPN MaCSBio, RS: FSE MaCSBio, Bioinformatica, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: HVC Pieken Maastricht Studie (9), and MUMC+: MA Interne Geneeskunde (3)
Background Worldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Results We report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton. Conclusions We present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals.